title: Infection duration and inflammatory imbalance are associated with atherosclerotic risk in HIV-infected never-smokers independent of antiretroviral therapy.
abstract: OBJECTIVE
  To determine whether the reported increased atherosclerotic risk among HIV-infected individuals is related to antiretroviral therapy (ART) or HIV infection, whether this risk persists in never-smokers, and whether inflammatory profiles are associated with higher risk.
  
  
  METHODS
  Matched cross-sectional study.
  
  
  METHODS
  A total of 100 HIV-infected patients (50 ART-treated >4 years, 50 ART-naive but HIV-infected >2 years) and 50 HIV-negative controls were recruited in age-matched never-smoking male triads (mean age 40.2 years). Carotid intima-media maximal thickness (c-IMT) was measured across 12 sites. Pro-inflammatory [highly sensitive C-reactive protein (hs-CRP), resistin, interleukin-6, interleukin-18, insulin, serum amyloid A, D-dimer) and anti-inflammatory (total and high molecular weight adiponectin, interleukin-27, interleukin-10) markers were dichotomized into high/low scores (based on median values). c-IMT was compared across HIV/treatment groups or inflammatory profiles using linear regression models adjusted for age, diabetes, hypertension, and, for HIV-infected patients, nadir CD4 cell counts.
  
  
  RESULTS
  Although adjusted c-IMT initially tended to be thicker in ART-exposed patients (P=0.2), in post-hoc analyses stratifying by median HIV duration we observed significantly higher adjusted c-IMT in patients with longer (>7.9 years: 0.760±0.008 mm) versus shorter prevalent duration of known HIV infection (<7.9 years: 0.731±0.008 mm, P=0.02), which remained significant after additionally adjusting for ART (P=0.04). Individuals with low anti-inflammatory profile (<median versus >median score) had thicker c-IMT (0.754±0.006mm versus 0.722±0.006 mm, P<0.001), with anti-inflammatory markers declining as prevalent duration of HIV infection increased (P for linear trend <0.001).
  
  
  CONCLUSIONS
  Known HIV duration is related to thicker c-IMT, irrespective of ART, in these carefully selected age-matched never-smoking HIV-treated and ART-naive male individuals. Higher levels of anti-inflammatory markers appeared protective for atherosclerosis.
authors.affiliation: aDepartment of Epidemiology, Columbia University, Mailman School of Public Health, New York, USA bInserm U-738 and École des Hautes Études en Santé Publique cAP-HP Department of Cardiology, Hôpital Saint-Antoine, F-75012, Paris, France dUPMC Univ Paris 06, Paris F75012 eAPHP Department of Infectious and Tropical Diseases, Hôpital Saint-Antoine fAPHP Hôpital Tenon, Service de biochimie et hormonologie, Paris F75020 gInserm UMR_S938, Paris F-75012 hInserm U970, Paris-Cardiovascular Research Center, and Paris-Descartes University iAP-HP Centre d'Investigation Clinique Paris-EST (9304), Hôpital Pitié-Salpêtrière, Paris, France jDepartment of Medicine, University of Cambridge, Cambridge, UK kInserm UMR-S707, Paris, France.
authors.forename: Moïse
authors.initials: M
authors.lastname: Desvarieux
authors.forename: Franck
authors.initials: F
authors.lastname: Boccara
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Meynard
authors.forename: Jean-Phillipe
authors.initials: JP
authors.lastname: Bastard
authors.forename: Ziad
authors.initials: Z
authors.lastname: Mallat
authors.forename: Beny
authors.initials: B
authors.lastname: Charbit
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Demmer
authors.forename: Nabila
authors.initials: N
authors.lastname: Haddour
authors.forename: Soraya
authors.initials: S
authors.lastname: Fellahi
authors.forename: Alain
authors.initials: A
authors.lastname: Tedgui
authors.forename: Ariel
authors.initials: A
authors.lastname: Cohen
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Capeau
authors.forename: Anders
authors.initials: A
authors.lastname: Boyd
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D050197:Atherosclerosis / Q000453:epidemiology*; D002097:C-Reactive Protein / Q000032:analysis*; D059168:Carotid Intima-Media Thickness; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D012307:Risk Factors; D013997:Time Factors
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D002097:C-Reactive Protein